This COBRE Phase III renewal is aimed at sustaining the research infrastructure built during the first ten years of NCRR funding. Our COBRE Cardiovascular Developmental Biology Center has become a nationally recognized, collaborative center with exclusive strengths in developmentally-related, cardiovascular diseases. Three underlying themes define the Center's research: understanding mechanisms of normal and abnormal heart and vascular development; investigating the developmental basis of adult cardiovascular diseases; and applying the principles of normal cardiovascular developmental biology to regenerative medicine or stem cell-based, tissue engineering. COBRE accomplishments towards these three cradle to grave goals include the recruitment of 8 new faculty, mentoring and training of 23 COBRE target faculty, and the development of 3 research core facilities. Programmatic outcomes include 28 independent research awards to target faculty, >410 peer reviewed publications, the State of South Carolina Center of Economic Excellence (COEE) awarding six endowed chairs in Regenerative Medicine and Advanced Tissue Biofabrication shared in partnerships with Clemson and the University of South Carolina, an NSF Research Infrastructure Improvement award to establish a statewide alliance in tissue fabrication, participation in the successful renewal of a statewide INBRE award in regenerative medicine, and funding of a translational award by the Leducq Foundation to create a Transatlantic Research Network exploring genetic mechanisms for valve diseases. For this PSO application, the plan for the Center transitioning to being independent of NIH/NCRR support during the next five years is to enhance and upgrade our core technologies, to increase their competitiveness to attract greater usage (and cost recovery), and to promote new research collaborations with our Center that can lead to submission of competitive research applications and broaden our statewide outreach, especially to other IDeA centers. A ten Step, five year strategic plan including implementing fee structures, pilot projects, outreach activities and programmatic development is proposed to sustain the CDBC/COBRE center and its three scientific cores (Morphology, Imaging and Instrumentation Core, Proteogenomics and Bioinformatics Core, and Gene Function Core). An Administrative Core, led by the founding director of MUSC's Cardiovascular COBRE, is home to the Program Coordinator and the Internal Advisory Committee. Together, they will act as the main operational arm of the Center. An External Advisory Committee will provide ongoing assessment and evaluation of the Center's progress. Institutional commitments from the Associate Provost for Research and Dean of the College of Medicine - exceeding one million dollars - help ensure programmatic growth development, and long-term sustainability of the Center.